chr16-30188392-C-A

Position:

chr16-30188392-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007074.4(CORO1A):c.1097C>A(p.Pro366His) variant causes a missense change. The variant allele was found at a frequency of 0.00295 in 1,613,852 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0030 ( 14 hom. )

Consequence

CORO1A
NM_007074.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.75

Variant links:

Genes affected

CORO1A (HGNC:2252): (coronin 1A) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. A related pseudogene has been defined on chromosome 16. [provided by RefSeq, Sep 2010]

CORO1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01099515).

BP6

Variant 16-30188392-C-A is Benign according to our data. Variant chr16-30188392-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 541422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30188392-C-A is described in Lovd as [Likely_benign]. Variant chr16-30188392-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00253 (386/152302) while in subpopulation NFE AF= 0.00354 (241/68022). AF 95% confidence interval is 0.00318. There are 0 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORO1A	NM_007074.4 linkuse as main transcript	c.1097C>A	p.Pro366His	missense_variant	10/11	ENST00000219150.10	NP_009005.1
CORO1A	NM_001193333.3 linkuse as main transcript	c.1097C>A	p.Pro366His	missense_variant	11/12		NP_001180262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORO1A	ENST00000219150.10 linkuse as main transcript	c.1097C>A	p.Pro366His	missense_variant	10/11	1	NM_007074.4	ENSP00000219150	P1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00301

AC:

752

AN:

250000

Hom.:

AF XY:

0.00301

AC XY:

407

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.0213

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00384

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00300

AC:

4381

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

2133

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.0209

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00213

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00334

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152302

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00354

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00378

Hom.:

Bravo

AF:

0.00240

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00287

AC:

349

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	CORO1A: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Severe combined immunodeficiency due to CORO1A deficiency

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

CORO1A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

.;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.68

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.027

D;D

Polyphen

0.93

P;P

Vest4

0.34

MVP

0.30

MPC

1.9

ClinPred

0.043

GERP RS

5.8

Varity_R

0.13

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over